One of the most frustrating facets of cancer biology is that secondary tumor metastases can lie dormant until activated by a suitable stimulus. This stimulus is often the surgical removal of a primary tumor. Primary tumors secrete antiangiogenic factors that decrease angiogenesis in secondary tumors, and thereby inhibit their growth. See, e.g., Sckell et al., CANCER RESEARCH 58:5866-5869 (1998) and Guba et al., CANCER RESEARCH 61:5575-5579 (2001). Removal of the primary tumor withdraws these antiangiogenic inhibitors and allows the secondary tumors to proliferate.
Inducing primary and secondary tumor cells to migrate towards a source of chemoattractant could be used as a means to isolate an invasive cell population. This would be especially effective for the treatment of glioblastoma, the most aggressive and universally fatal human brain tumor.
Every year 15,000 new cases of glioblastoma are diagnosed in the United States. More than 75% of these patients will die within two years following their initial diagnosis, even after administration of the standard triple therapy of surgical resection, radiation, and chemotherapy. See, e.g., Stupp et al., ONKOLOGIE 28(6-7):315-7 (2005).
Current treatment of glioblastoma includes surgical resection of the tumor mass followed by radiation in the vicinity of the resection cavity (usually 1-2 cm around) (Stupp et al., THE NEW ENGLAND JOURNAL OF MEDICINE 352(10):987-96 (2005)) and administration of temozolomide (Stupp et al., ONKOLOGIE 28(6-7):315-7 (2005)). Even with this multi-therapeutic approach, tumor recurrence is inevitable (Wick et al., NEURO-ONCOLOGY 13(6):566-79 (2011)). This is due to the migration properties of the tumor cells, which invade the brain parenchyma creating multiple finger-like projections within the brain (Friedl et al., NATURE REVIEWS CANCER 3(5):362-74 (2003)) that make their elimination virtually impossible. It is evident that even after decades of intense clinical and basic research an efficient treatment for glioblastoma does not exist and a diagnosis of glioblastoma is still a terminal diagnosis.
Methods for isolating and sequestering motile cells have been described. U.S. Patent Application Publication No. 2013/0172846 to Bellamkonda et al. relates to a device having one or more surface structures which provide physical guidance cues for directing the migration of tumor cells from a first tissue location to a selected second location. U.S. Patent Application Publication No. 2011/0020216 to Mooney et al. pertains to a device capable of capturing, and therefore sequestering, undesirable cells, either within an internal compartment or along its external surface by either filtering cells through pores in the external surface or binding cells to adhesive proteins along either its internal or external surfaces. U.S. Patent Application Publication No. 2010/0124573 to Naughton et al. relates to methods of using extracellular matrix (ECM) compositions for the inhibition of growth or proliferation of cancers alone or as a biological vehicle for the delivery of a chemotherapeutic agent. U.S. Patent Application Publication No. 2012/0322685 to Condeelis et al. pertains to a method of isolating motile cells from an animal tissue comprising implanting in the animal tissue a cell trap comprising at least one chamber with an inlet for ingress of motile cells, and a porous matrix located in the chamber comprising a chemotactic factor, for a time sufficient for the motile cells to migrate into the cell trap, removing the implanted cell trap, and retrieving the motile cells from the cell trap. Williams et al., PROCEEDINGS OF SPIE 8251:1-7 (2012), pertains to an optically transparent, implantable tool to study the tumor microenvironment loaded with a hydrogel that is implanted into a tumor. Wang et al., BIOMATERIALS 30(36):6986-95 (2009) pertains to an immunocyte delivery platform with which cell-based immunotherapy can be initiated at a desired location and implemented in a controlled manner. However, these methods suffer from several disadvantages, including non-biocompatibility of physical devices and lack of effective chemoattractants.
Accordingly, described herein are new systems and methods for attracting and trapping brain cancer cells that are safer and more effective than currently-available modalities.